Pregnancy and sickle cell disease: A review of the current literature
Introduction
Sickle cell disease (SCD) is caused by a homozygous mutation in hemoglobin S and presents as chronic anemia accompanied by severely painful episodes. The principal defect triggering disease signs and symptoms is impaired microcirculation caused by sickling of rigid erythrocytes (vaso-occlusion) (Archer et al., 2015). Heterozygous combinations of hemoglobin S with other abnormal hemoglobins (HbSC, HbSE, HbS-beta o-thalassemia, and HbSD) are other clinical conditions causing painful episodes and tissue injury (Archer et al., 2015, Sheth et al., 2013).
SCD is one of the most common hereditary diseases, and affects approximately 30 million patients worldwide. The global number of neonates affected by HbS in 2010 included 312,000 SS neonates> (Piel et al., 2013). A total of 70,000 SCD patients live in the USA (Parrish and Morrison, 2013). The disease is common among Afro-Americans, being evident in 1 in every 500 live births. Approximately 12,000–15,000 SCD patients live in France, and 400 new patients are born there every year (Sheth et al., 2013). In England, approximately 200 SCD pregnancies occur annually (Sheth et al., 2013). Although the childhood mortality risk has been reduced by advances in patient care and supportive therapy, the risk of death is higher in adults than children, and the mean lifespan of U.S SCD population is only 39 years (Sheth et al., 2013). The mean age of patients who died in our center over the past 10 years was 36 years (unpublished data).
Studies have shown that If pregnancy occurs in women with SCD, patients had a risk of maternal and fetal complications (Parrish and Morrison, 2013, Rogers and Molokie, 2010). However, limited comprehensive data on maternal or fetal mortality during pregnancy are available. This is because, first, the clinical course of SCD is extremely variable even within patients of the same family. Second, patient care has evolved over time. Third, the level of patient care varies worldwide. This review aims to provide an extensive descriptive review of studies published on this topic, to summarise current knowledge for comprehensive maternal and perinatal outcomes in pregnant women with SCD, and to propose recommendations which can contribute to the management of the pregnancies complicated by disease.
References for this review were identified through a PubMed search that included the period from 2005 until 20th August 2015. The term “sickle cell” was crossed with “pregnancy or pregnant”, “maternal mortality”, “obstetrics”, “fetus”, “antenatal”, and “prenatal”. This search retrieved 790 references that were examined one-for-one, with those strictly related to management of pregnancy in SCD (n = 57) selected. Eligibility of the original papers and review articles were inspected by two authors (C.B., H.O).
Studies were selected for this review if study population consisted of women with SCD disease; maternal and/or perinatal outcomes were included; studies used population-based linked data system; study design was systematic review, metaanalysis, national cohort study, randomized trial and/or case control study. Exclusion criteria consisted of studies without a comparator group, editorial and letters without sufficient data, case reports, and studies including women with sickle cell trait.
Section snippets
The role played by pregnancy in SCD pathophsiology
Both the SCD mother and baby are at increased risk of adverse events during pregnancy. Such risks evolve from increases in metabolic demand, the tendency toward coagulation, and vascular stasis (Seaman et al., 2014). Endothelial activation triggers inflammation caused by cytokines, and activation of the coagulation system (Ozdogu et al., 2007). Chronic hemolysis aggravates pre-existing impairments in microvascular circulation (Sheth et al., 2013, Anon, 2011, Curuk et al., 2008).
General/family practice evaluation
Information on the risks associated with pregnancy, and advice and support seeking to optimize general health, should be offered to all women and men of childbearing age to reduce reproductive risk and improve pregnancy outcomes (Evidence-Based Management of Sickle Cell Disease, 2014). Hemoglobin electrophoresis of the mother and father, coupled with genetic counseling, are the principal features of preconceptual care (Howard and Oteng-Ntim, 2012, Porter et al., 2014a). If the mother has SCD,
The obstetrician
Hemoglobin electrophoresis and/or partner genetic tests should be run if such tests were not performed prior to conception, and should be evaluated by a perinatologist, who must plan prenatal tests if the partner is a carrier. Interventional methods including a chorionic villus biopsy at 10–13 weeks of gestation, or amniocentesis at 15–16 weeks, may be required to facilitate diagnosis. Fetal blood samples may be obtained after week 20 of gestation; however, this is associated with a high risk
Intrapartum care
Despite the lack of controlled studies, delivery is recommended at gestational weeks 38–40, as longer pregnancies may increase complications associated with SCD and pregnancy per se, and trigger fetal growth retardation. No medical complication has been reported after normal vaginal delivery. The general medical indications for cesarean section patients are valid in those with SCD (Howard and Oteng-Ntim, 2012). General anesthesia should be avoided because of the increased risk of (for example)
Postpartum care
The mother should give birth at a hospital that has an intensive care unit.
The incidences of anorexia, nausea, urinary tract infection, wound infection, endometritis, and venous thromboembolism are higher in mothers who deliver via cesarean section (≥3%) compared to normal vaginal delivery (Seaman et al., 2014). Prophylaxis with low-molecular-weight heparin should be discontinued 24 h prior to delivery and recommenced 12 h thereafter. Low-molecular-weight heparin should be maintained to 6 weeks
Management of a pain crisis during pregnancy
Painful episodes that require hospitalization occur frequently in females with SCD; the incidence is approximately 50% in patients with the SS, Sβ0, and Sβ+ genotypes; and 20–30% in those with the SC genotype (Parrish and Morrison, 2013, Porter et al., 2014a). Crises are more frequent in the third trimester (Archer et al., 2015). Patients who develop a pain crisis or who are under suspicion of such a crisis during pregnancy should be hospitalized. Bed rest and adequate fluid intake are
Lessons from previous studies
Existing reports do not adequately illustrate the course of pregnancy in SCD patients; no prospective controlled trials have been conducted. Most data were retrospectively excerpted from formal reports, which may or may not have been audited. The conduct of controlled trials would facilitate the creation and implementation of Standard Operating Procedures (SOPs) guiding pregnancy management in SCD patients, and would eliminate among-center variations in patient care. The dissemination of
Conflict of interest
The authors of this paper have no conflict of interest, including specific financial interests, relationship, and/or affiliations relevant to the subject matter or materials included.
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Professor Can Boga, and Professor Hakan Ozdogu are hematologist. They have worked at the Baskent University since 11 years. Their current positions are Medical Clinical Director and Clinical Director in Baskent University Adana BMT Center, respectively. They have twenty years of experience in the care of patients with SCD living in the Mediterranean region of Turkey. Their last article on SCD during pregnancy was published in Transfusion in July 2014.